A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection,Science

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A multivalent mRNA-LNP vaccine protects against Clostridioides difficile infection
Science ( IF 44.7 ) Pub Date : 2024-10-03 , DOI: 10.1126/science.adn4955
Mohamad-Gabriel Alameh, Alexa Semon, Nile U. Bayard, Yi-Gen Pan, Garima Dwivedi, James Knox, Rochelle C. Glover, Paula C. Rangel, Ceylan Tanes, Kyle Bittinger, Qianxuan She, Haitao Hu, Srinivasa Reddy Bonam, Jeffrey R. Maslanka, Paul J. Planet, Ahmed M. Moustafa, Benjamin Davis, Anik Chevrier, Mitchell Beattie, Houping Ni, Gabrielle Blizard, Emma E. Furth, Robert H. Mach, Marc Lavertu, Mark A. Sellmyer, Ying Tam, Michael C. Abt, Drew Weissman, Joseph P. Zackular

Clostridioides difficile infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)–lipid nanoparticle (LNP) vaccine targeting C. difficile toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic C. difficile from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel C. difficile therapeutics with potential for limiting acute disease and promoting bacterial decolonization.

更新日期：2024-10-03

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